Rapid and Simultaneous Initiation of Four Guideline-Directed CKD Therapies (RAPID-CKD)

Официальное название

A Pilot Randomized Clinical Trial to Assess Feasibility, Safety, and Efficacy of Rapid, Simultaneous Therapy Initiation in Chronic Kidney Disease and Type 2 Diabetes: RAPID-CKD

Обзор

The goal of this clinical trial is to learn if starting four kidney disease medicines quickly and together (a rapid treatment approach) is safe and works well in people with type 2 diabetes and chronic kidney disease. The main questions it aims to answer are: * Is it safe to start these medicines over a short period of time? * How often do kidney function changes or high potassium levels occur? * Does this approach lower protein in the urine (a sign of kidney damage)? * How many participants are able to stay on all four medicines over 6 months? Researchers will compare this approach to usual care, where medicines are started one at a time over several months. Participants will: Be assigned by chance to either this approach or usual care Start up to four approved kidney medicines over about 8 weeks (rapid treatment approach) or follow standard care Have regular clinic visits and lab tests to check kidney function and potassium levels Be followed for about 6 months

Подробное описание

This study is a pilot, open-label, randomized clinical trial designed to evaluate the feasibility, safety, and effectiveness of rapidly starting multiple guideline-recommended therapies in people with type 2 diabetes and chronic kidney disease.

In current clinical practice, these medicines are usually started one at a time over many months. This step-by-step approach may delay potential benefits and leave people at continued risk of kidney disease progression and cardiovascular complications. This study will test a different approach, where these therapies are started in a structured and closely monitored way over a short period of time.

Participants will be randomly assigned to either a rapid initiation strategy or usual care. In the rapid group, up to four approved therapies will be started and adjusted over approximately 8 weeks using a structured treatment plan. In the usual care group, treatment will follow standard clinical practice, where medications are introduced gradually at the discretion of the treating clinician.

Participants in both groups will be followed for 6 months. During this time, they will have regular clinic visits and laboratory testing to monitor kidney function, potassium levels, and overall treatment tolerance.

This pilot study will provide important information on whether this rapid treatment approach can be safely implemented in real-world clinical settings and whether participants are able to start and continue multiple therapies within a short time frame.

Вмешательства

• Препарат Finerenone
  10-40mg daily
• Препарат Semaglutide
  .25-1.0mg 1 time a week
• Препарат Lotensin
  10-40mg daily
• Препарат Capoten
  12.5-50mg 3 times a day
• Препарат Enalapril
  2.5-10mg daily
• Препарат Monopril
  10-40mg daily
• Препарат Lisinopril
  5-20mg daily
• Препарат Univasc
  3.75-15mg daily
• Препарат Aceon
  4-16mg daily
• Препарат Accupril
  10-40mg daily

Первичные конечные точки

• On-study retention rate at 6 months [Срок оценки: 6 months]
• Sustained decline in eGFR ≥30% [Срок оценки: 6 months]
• Change in UACR [Срок оценки: 6 months]

Вторичные конечные точки (12)

• Enrollment rate [Срок оценки: 6 months]
• Protocol adherence [Срок оценки: 6 months]
• Treatment discontinuation [Срок оценки: 6 months]
• Moderate Hyperkalemia [Срок оценки: 6 months]
• Severe Hyperkalemia [Срок оценки: 6 months]
• Acute Kidney Injury [Срок оценки: 6 months]
• End-stage kidney disease [Срок оценки: 6 months]
• Number of participants with permanent drug discontinuation [Срок оценки: 6 months]
• Rate of change in estimated glomerular filtration rate (slope) [Срок оценки: 6 months]
• Change in glycated hemoglobin (HbA1c) [Срок оценки: 6 months]
• Number of participants who achieve >30% reduction in urine albumin-to-creatinine ratio [Срок оценки: 6 months]
• Change in Kidney Disease Quality of Life-36 score [Срок оценки: 6 months]

Критерии участия

Критерии включения

• Patients aged 18-84 years
• eGFR 45 to ≤90 mL/min/1.73 m2
• UACR >200 mg/g
• diagnosis of T2D
• receiving ≤2 guideline-recommended drug classes irrespective of dose for ≥4 weeks prior to screening
• eligible for all 4 drugs
• systolic BP (SBP) >90 mmHg
• those willing to provide written informed consent and to adhere to study visits.

Критерии исключения

• Type 1 diabetes
• any known primary non-diabetic kidney disease (i.e., polycystic kidney disease, glomerulonephritis, interstitial nephritis, etc.)
• history of kidney transplant
• liver disease (i.e., aspartate transaminase or alanine transaminase >5 times, or bilirubin >3 times the upper limit of normal)
• serum potassium >5.5 mEq/L at baseline
• known hypersensitivity to any study drug
• life expectancy <6 months
• active malignancy or infection
• brittle diabetes (defined as severe glycemic instability with hospitalization or emergency care for hypoglycemia or hyperglycemia within the past 6 months)
• high-risk of hypoglycemia (Clarke or Gold score ≥4)
• predicted 12-month risk of hypoglycemia related emergency visits or hospitalizations >5% using the Kaiser Permanente hypoglycemia prediction score
• high dose insulin use (>1 unit/kg/day).
• RASi: hyperkalemia or angioedema
• SGLT2i: diabetic ketoacidosis, type 1 diabetes, recurrent genitourinary infections
• ns-MRA: hyperkalemia
• GLP1-RA: personal or family history of medullary thyroid carcinoma, known gastroparesis, or pancreatitis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Baylor Scott and White Medical Center- Temple — Temple

Публикации

• Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022 Apr;12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. Epub 2022 Mar 18. PMID 35529086
• Dalrymple LS, Katz R, Kestenbaum B, Shlipak MG, Sarnak MJ, Stehman-Breen C, Seliger S, Siscovick D, Newman AB, Fried L. Chronic kidney disease and the risk of end-stage renal disease versus death. J Gen Intern Med. 2011 Apr;26(4):379-85. doi: 10.1007/s11606-010-1511-x. Epub 2010 Sep 19. PMID 20853156
• Collins AJ, Li S, Gilbertson DT, Liu J, Chen SC, Herzog CA. Chronic kidney disease and cardiovascular disease in the Medicare population. Kidney Int Suppl. 2003 Nov;(87):S24-31. doi: 10.1046/j.1523-1755.64.s87.5.x. PMID 14531770
• Khan MS, Rashid AM, Shafi T, Rangaswami J, Cherney DZI, Butler J. Residual Risk of Adverse Kidney and Cardiovascular Outcomes in Patients with CKD. Clin J Am Soc Nephrol. 2025 Mar 1;20(3):451-454. doi: 10.2215/CJN.0000000588. Epub 2024 Dec 17. No abstract available. PMID 39688924
• Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24. PMID 38785209
• Mayer GJ, Wanner C, Weir MR, Inzucchi SE, Koitka-Weber A, Hantel S, von Eynatten M, Zinman B, Cherney DZI. Analysis from the EMPA-REG OUTCOME(R) trial indicates empagliflozin may assist in preventing the progression of chronic kidney disease in patients with type 2 diabetes irrespective of medications that alter intrarenal hemodynamics. Kidney Int. 2019 Aug;96(2):489-504. doi: 10.1016/j.kint.2019. PMID 31142441
• Neuen BL, Oshima M, Perkovic V, Agarwal R, Arnott C, Bakris G, Cannon CP, Charytan DM, Edwards R, Gorriz JL, Jardine MJ, Levin A, Neal B, De Nicola L, Pollock C, Rosenthal N, Wheeler DC, Mahaffey KW, Heerspink HJL. Effects of canagliflozin on serum potassium in people with diabetes and chronic kidney disease: the CREDENCE trial. Eur Heart J. 2021 Dec 21;42(48):4891-4901. doi: 10.1093/eurheartj/eha PMID 34423370
• Brownell NK, Ziaeian B, Fonarow GC. The Gap to Fill: Rationale for Rapid Initiation and Optimal Titration of Comprehensive Disease-modifying Medical Therapy for Heart Failure with Reduced Ejection Fraction. Card Fail Rev. 2021 Nov 26;7:e18. doi: 10.15420/cfr.2021.18. eCollection 2021 Mar. PMID 34950508

Идентификаторы

NCT: NCT07547878 · 026-271

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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